title: Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of >40 000 patients.
abstract: OBJECTIVE
  Statin therapy is associated with important benefits for patients at risk of, and with, established cardiovascular disease. There is widespread interest in whether intensive dosing of statins yields larger treatment effects. We aimed to determine if intensive dosing is clinically important using a meta-analysis of randomized clinical trials (RCTs).
  
  
  METHODS
  We conducted comprehensive searches of electronic databases from inception to December 2010. We included any RCT evaluating a larger dose with a clinically common dose. Two reviewers independently extracted data, in duplicate. We performed random-effects meta-analysis and a trial sequential analysis.
  
  
  RESULTS
  We identified 10 RCTs enrolling a total of 41 778 participants. Trials followed patients for a mean of 2.5 years. We did not find statistically significant effects on all-cause mortality [relative risk (RR) 0.92, 95% confidence interval (CI), 0.83-1.03, P = 0.14, I(2) = 38%] or cardiovascular disease (CVD) deaths (RR 0.89, 95% CI, 0.78-1.01, P = 0.07, I(2) = 34%). When we pooled the composite endpoint of coronary heart disease (CHD) death plus non-fatal myocardial infarction (MI), we found a significant protective effect of intensive statin dosing (RR 0.90, 95% CI, 0.84-0.96, P ≤ 0.0001, I(2) = 0%). We also found a significant effect on non-fatal MIs (RR 0.82, 95% CI, 0.76-0.89, P ≤ 0.0001, I(2) = 0%) and a significant reduction in the composite of fatal and non-fatal strokes (excluding transient ischaemic attacks) reported in 10 RCTs (RR 0.86, 95% CI, 0.77-0.96, P = 0.006, I(2) = 0%). A subgroup analysis of three trials examining acute coronary syndrome patients found significant effects on all-cause (RR 0.75, 95% CI, 0.61-0.91, P = 0.005, I(2) = 0%) and CVD mortality (RR 0.74, 95% CI, 0.59-0.94, P = 0.013, I(2) = 0%) with intensive dosing. Applying an analysis of optimal information size on the primary analysis, we found that the evidence for CHD death plus non-fatal MIs is conclusive. The evidence for CVD deaths alone is not yet conclusive.
  
  
  CONCLUSIONS
  Available evidence suggests that intensive statin therapy reduces the risk of non-fatal events and may have a role in reducing mortality.
authors.affiliation: Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada V5Z 4B4 K1n6X1. edward.mills@uottawa.ca
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Mills
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Regan
authors.forename: Oghenowede
authors.initials: O
authors.lastname: Eyawo
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.forename: Fergal
authors.initials: F
authors.lastname: Mills
authors.forename: Otavio
authors.initials: O
authors.lastname: Berwanger
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
mesh_terms: D054058:Acute Coronary Syndrome / Q000401:mortality; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D002423:Cause of Death; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D015588:Observer Variation; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors